title: Influence of chitosan glutamate on the in vivo intranasal absorption of rokitamycin from microspheres.
abstract: Intranasal delivery is an alternative method to target therapeutics to the central nervous system. In the present study, chitosan glutamate (CG)-based mucoadhesive microspheres containing rokitamycin (RK) were prepared by spray-drying and in vitro characterization. Moreover, the influence of CG on RK absorption in bloodstream and cerebrospinal fluid (CSF) was evaluated after nasal administration to rats. The in vivo results were compared with those obtained after nasal administration of chitosan (CH)-based microparticles containing RK and after intravenous (IV) administration of the free drug. The in vitro results indicate that the concentrations of feed solution or kind of CH influence the RK entrapment and size of microspheres. All formulations increase the solubility of this poorly water-soluble drug, but CG is more able to increase the in vitro dissolution rate of RK than CH. CG microspheres absorb water quickly and then dissolve, whereas CH particles need more volume of water for swelling and gelling. In vivo studies showed that, after IV administration, RK is not able to cross the blood-brain barrier and to reach the CSF from the bloodstream. On the contrary, drug goes to the CSF and the bloodstream only after nasal administration of CG microparticles.
authors.affiliation: Department of Drug Sciences, University of Sassari, Sassari 07100, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gavini
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rassu
authors.forename: Luca
authors.initials: L
authors.lastname: Ferraro
authors.forename: Amanda
authors.initials: A
authors.lastname: Generosi
authors.forename: Julietta V
authors.initials: JV
authors.lastname: Rau
authors.forename: Antonio
authors.initials: A
authors.lastname: Brunetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Giunchedi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Dalpiaz
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry*; D006801:Humans; D008297:Male; D008863:Microspheres; D015644:Miocamycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D065588:Nasal Absorption; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D018698:Glutamic Acid; D015644:Miocamycin; D048271:Chitosan; C033383:rokitamycin
keywords: CNS; brain targeting; chitosan; controlled release/delivery; in vivo studies; microspheres; nasal drug delivery; rokitamycin; site-specific delivery; spray drying